Patients Overly Optimistic About Phase I Clinical Trials

Personality traits may influence a patient's expectation of clinical benefit from a Phase I clinical trial, according to a multi-center study, which included the Johns Hopkins Bloomberg School of Public Health, Duke University and other institutions. The researchers believe that understanding how these personality traits influence a patient’s decision to participate in a clinical trial could help identify problematic areas in the informed consent process. The study was published in the July 1, 2003, issue of the journal Cancer.

Phase I clinical trials are designed primarily to show the safety of a therapy rather than to test for clinical benefit. Historically, fewer than five percent of patients respond to experimental therapies in a Phase I trial. Because the patient’s correct understanding of the treatment or clinical trial is a key element of the informed consent process, the researchers were concerned that patients with high expectations for clinical benefit might not grasp the true purpose and potential risks of the trial.

“Many patients operate under what has been called a ‘therapeutic misconception’ that Phase I clinical trials are designed to provide them with personal benefit,” said Kevin Weinfurt, PhD, deputy director, Center for Clinical and Genetic Economics at Duke University Medical Center and lead author of the study. “We are trying to understand how, even with extensive counseling, patients continue to express high expectations. Once we know what’s behind these statements, perhaps we can address them in the consent process.”

The study aimed to understand the type of patient who believes strongly that he or she will benefit. In the study, the researchers surveyed 260 cancer patients enrolling in Phase I clinical trials about their expectations regarding the chance that their disease would be controlled by the experimental therapy studied in the trial. Survey participants all had advanced cancer for which there was either no standard effective therapy or standard therapy failed.

The authors’ analysis focused on a subset of the 121 survey items, which were developed as part of a larger study, led by Neal Meropol, MD, of Fox Chase Cancer Center, on patients’ decision to participate in Phase I clinical trials. Items used in Dr. Weinfurt’s study included questions about how optimistic the patients considered themselves, their willingness to take monetary risks and their ability to understand a statistical statement about benefit; for example, “What does it mean if a physician says that some new treatment will control cancer in 40 percent of cases like yours?”

The survey demonstrated that patients who were more likely to express a high expectation of clinical benefit reported better health-related quality of life, stronger religious faith, greater optimism, a willingness to take monetary risks and had a slightly poorer understanding of a statistical statement about the chance of benefit. Expectations of clinical benefit were similar among patients, regardless of age, gender, living situation, education level or severity of symptoms.

“Most of the survey responses were skewed toward higher expectations,” said Dr. Weinfurt. “A large percentage of patients reported that they had an 80 to 100 percent chance of positive clinical response. But the greatest spike was in the number of patients that reported that they believed they had a 50 percent chance of clinical benefit.”

Nearly a quarter of patients surveyed reported that they believed they had a 50 percent chance of the therapy working for them; approximately ten times more than the actual probability (five percent). Dr. Weinfurt said this 50 percent response might be based on the “pseudo logic” that the treatment will either work or it will not work, so therefore they have a 50/50 chance of benefit. Also, he said, some patients might not have thought about their chances in numerical terms, so they simply chose the figure in the middle.

“We were also surprised to find that patients who reported high expectations that they would receive clinical benefit from the trial also had high expectations of the level of benefit. These patients believed the chance of benefit was high, and that the maximum type of benefit they could experience would be very dramatic,” said Dr. Weinfurt.

The researchers said additional research is needed to learn when such high expectations of benefit reflect a misunderstanding and when they might represent something else.

Darrell Gaskin, PhD, research scientist in the School’s Department of Health Policy and Management, said, “Patient optimism regarding the therapeutic benefits of experimental therapies is not randomly distributed. This study shows that cancer patients’ expectations of benefit from experimental therapy are strongly correlated with quality of life, relative health stock and personality variables such as religious faith, optimism, monetary risk and poorer numeracy. The impact of patient optimism on the outcomes of these experimental studies is unknown. Future studies are needed to understand the psycho-social consequences of having high expectations.”

Co-authors in the study were Kevin Schulman, Liana Castel and Yun Li, of Duke University Medical Center; Daniel Sulmasy, Saint Vincent Catholic Medical Centers and the Bioethics Institute of New York Medical Colleg;, Andrew Balshem, Elyse Slater and Neal Meropol, all of Fox Chase Cancer Center; Al Benson III, Northwestern University; Caroline Burnett and John Marshall, Georgetown University; and Darrell Gaskin, Johns Hopkins Bloomberg School of Public Health.

Duke University’s complete press release can be viewed by visiting http://dukemednews.org/news/article.php?id=6683.